Phthalimide → (1S,2S,5R)-2-(3-benzyl-7,7-difluoro-3-azabicyclo[3.3.0]oct-2-ylmethyl)-isoindole-1,3-dione

HRID 425804Notes

Reaction equation

HRID 425804 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[C:32]1(=[O:42])[NH:36][C:35](=[O:37])[C:34]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:33]12.[CH2:43]([N:50]1[CH2:57][CH:56]2[CH:52]([CH2:53][C:54]([F:59])([F:58])[CH2:55]2)[CH:51]1[CH2:60]O)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C1COCC1.C1(C)C=CC=CC=1.CC(=O)OCC.CCCCCCC.CC(=O)OCC>[CH2:43]([N:50]1[CH2:57][C@H:56]2[C@H:52]([CH2:53][C:54]([F:59])([F:58])[CH2:55]2)[C@H:51]1[CH2:60][N:36]1[C:32](=[O:42])[C:33]2[C:34](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:35]1=[O:37])[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

9

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 66703990(3-Benzyl-7,7-difluoro-3-azabicyclo[3.3.0]oct-2-yl)-methanol

Product 1

HCID 59411625(1S,2S,5R)-2-(3-benzyl-7,7-difluoro-3-azabicyclo[3.3.0]oct-2-ylmethyl)-isoindole-1,3-dioneYield 64%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

To a cold solution of triphenylphosphine (1.8 g) in dry THF (90 mL) was added dropwise DEAD 40% in toluene (3.15 mL). Then was added successively phthalimide (1.01 g) and a solution of (3-benzyl-7,7-difluoro-3-azabicyclo[3.3.0]oct-2-yl)-methanol (WO03/062265) (1.83 g) in dry THF (10 mL). The reaction mixture was stirred at RT overnight, diluted with EA, washed with water. The organic phase was washed with sat. NaHCO3 solution, dried (MgSO4), filtered and concentrated to yield a crude oil. FC (n-heptane/EA: 7/3 to 1/1) gave 1.73 g (64%) of the title compound as a white solid. LC-MS: tR=0.87 min; [M+H]+=397.47.

Workup

  1. washwashed with water
  2. washThe organic phase was washed with sat. NaHCO3 solution
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield a crude oil

Sources & evidence

ORD record
ord-3d60d04688e7468f9739125c9dabb199
Source dataset
uspto-grants-2012_01
Patent number
US08106215B2

Reaction notes

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